A large number of biological and clinical protocols, among others, gene therapy, production of biological materials, and biological research, depend on the ability to elicit specific and high-level expression of genes encoding RNAs or proteins of therapeutic, commercial, or experimental value. A variety of expression systems have been developed, including regulated expression systems, involving allosteric on switches triggered by tetracycline, RU486 and ecdysone, as well as dimerization based on-off switches triggered by FK1012, FK-CsA, rapamycin and analogs thereof. See e.g. Clackson, "Controlling mammalian gene expression with small molecules" Current Opinion in Chemical Biology 1997, 1:210-218. Still, achieving a sufficiently high level of expression for clinical or other utility in genetically engineered cells in various contexts, including within whole organisms, has often been a limiting problem. Various approaches for addressing this problem, including the search for stronger transcriptional promoters or higher transfection efficiencies, have in many cases not met with success. Meanwhile, in various lines of research with transcription factors, promising results in transient transfection models have not been borne out with chromosomally integrated reporter gene constructs. Furthermore, overexpression of transcription factors is commonly associated with toxicity to the host cell. Despite those precedents, this invention takes a novel approach to the challenge of optimizing gene expression through new uses of, and new designs for, transcription factor proteins which are expressed within the engineered cells containing the target gene. The invention provides improved methods and materials for achieving high-level expression of a target gene in genetically engineered cells, including genetically engineered cells within whole organisms.